title: Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database.
abstract: BACKGROUND
  While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).
  
  
  METHODS
  We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.
  
  
  RESULTS
  Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5).
  
  
  CONCLUSIONS
  Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.
authors.affiliation: 1] Division of Urology, Department of Surgery, Duke University School of Medicine, Durham, NC, USA [2] Cancer Prevention, Detection and Control Program, Duke Cancer Institute, Durham, NC, USA [3] Section of Urology, Veterans Affairs Medical Center, Durham, NC, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Allott
authors.forename: M R
authors.initials: MR
authors.lastname: Abern
authors.forename: L
authors.initials: L
authors.lastname: Gerber
authors.forename: C J
authors.initials: CJ
authors.lastname: Keto
authors.forename: W J
authors.initials: WJ
authors.lastname: Aronson
authors.forename: M K
authors.initials: MK
authors.lastname: Terris
authors.forename: C J
authors.initials: CJ
authors.lastname: Kane
authors.forename: C L
authors.initials: CL
authors.lastname: Amling
authors.forename: M R
authors.initials: MR
authors.lastname: Cooperberg
authors.forename: P G
authors.initials: PG
authors.lastname: Moorman
authors.forename: S J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D016208:Databases, Factual; D003920:Diabetes Mellitus / Q000188:drug therapy; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin